Welcome to UD RESEARCH

This exciting magazine showcases the discoveries, inventions and scholarly excellence of UD's faculty, staff and students. Our latest issue highlights a variety of environmental research across the UD campus, with impacts locally and around the world. Keep up with UD's growing research enterprise.

Dare to be first.

At the University of Delaware, discovery, invention and innovation matter. We’re thinking big.

Mix human ingenuity, abundant resources and a location in a state known as an
incubator of global, entrepreneurial R&D, and you have Idea Leadership — a key UD characteristic and a pillar of the University’s new “Dare to be first” brand.

True to that brand, invention disclosures are on the rise at UD — up 60% from last year with support from our Office
of Economic Innovation and Partnerships (OEIP). Here, you’ll meet inventors who are planting ideas with “green” potential in more ways than one: helping the environment and growing new
businesses.

Engineering the perfect cell

﻿Eleftherios (Terry) Papoutsakis (right), Eugene du Pont Chair of Chemical Engineering, works with postdoctoral research fellow Stephan Lindsey in the lab at the Delaware Biotechnology Institute.

Imagine being able to create an ideal organism for producing biofuels and
chemicals from renewable resources: resistant to toxic chemicals, a fast grower
and producer, complete with only desired, beneficial bioprocessing
characteristics.

While it sounds almost too good to be true, Eleftherios (Terry) Papoutsakis,
Eugene du Pont Chair of Chemical Engineering at UD, has filed two invention
disclosures this year that put him at the forefront of this uncharted research
field.

A classical chemical engineer by undergraduate training, Papoutsakis, who joined
the UD faculty in 2007, explains that, typically, genes from different species
cannot mix, such as those from humans with those from dogs or camels, because
cells do not recognize or express the foreign DNA.

“Organisms recognize their own specific elements of DNA that control the
expression of the genes that produce proteins to do the desirable reactions or
to get the desirable cell properties,” Papoutsakis says.

“What we want to do is to be able to mix properties of microbes so you have a
variety of new, semi-synthetic microbes, each one doing different things
suitable for different applications.”

Seeing the most promise for his research in the green sector, Papoutsakis gives
the example of engineering a cell to be resistant to the toxic chemicals
required to make the biofuels he wants to produce.

“My goal is to create a new cell — a new biocatalyst — for this process that is not only able to produce the chemicals of the biofuel
that I desire, but also is very resistant to those chemicals, so that it does
not die and keeps producing.”

Papoutsakis is working to engineer one microbe so that it can recognize the DNA
from another microbe, to, in turn, be able to express genes and change the
programming of the cells.

He calls these gene combinations from different microbial species “alloys” and has discovered several different ways to integrate them into cells.

Through this integration, Papoutsakis is able to take the traits desired from
each organism — each with a different type of DNA — and mix them together.

In addition to biofuels, Papoutsakis says the research method could even
translate into the medical field or pharmaceutical industry, as it would allow
for the production of a better cell that could produce small organic molecules
for drug testing.

Papoutsakis leads a research group at the Delaware Biotechnology Institute at UD
focused on genomic and metabolic engineering studies of microbial systems, as
well as applications of stem-cell biotech- nology for the production of blood
cells.

His research contributions have been recognized by numerous awards, including
most recently, the 2010 International Metabolic Engineering Award and the 2010
Elmer Gaden, Jr. Award from the journal Biotechnology and Bioengineering. He
also is the inventor on more than 15 patents and patent applications.

Some people see bacteria as a deterrent to productivity. However, for two UD
researchers, the colonization of plants by Bacillis subtilis holds promise for
battling droughts and plant diseases and, ultimately, for increasing yield for
farmers in Delaware and, possibly, around the globe.

Janine Sherrier and Harsh Bais, both professors of plant and soil sciences based
at the Delaware Biotechnology Institute at UD, were sharing “eureka” moments from their research and realized they could achieve potentially
revolutionary results if they collaborated.

“We have diverse interests, but we also have a lot of common ground,” Bais says.

Sherrier works on a very well-defined system of legumes and bacteria known as
rhizobia that live inside the roots of these plants, while much of Bais’ work focuses on relating abiotic stress — chemical or physical factors, such as drought — to plant structure, behavior and function.

According to Bais, plants and some bac-teria have evolved together to have
benefi­cial interactions.

“We have shown in the past that plants can actually recruit beneficial microbes,” he says.

Thus, when a plant is in distress, it sends a chemical signal; beneficial
bacteria react and aid the plant. While using the plant as their energy source,
the bacteria help fend off dangers and promote healthy plant growth.

Sherrier focuses her research efforts on biological nitrogen fixation in
legumes.

“In the lab, we are trying to define the components that are necessary for a
plant and a bacterium to recognize each other and form a symbiotic infection,” she says.

During a successful interaction between bacteria and legume roots, the bacteria
convert atmospheric nitrogen into a form that the plant utilizes for robust
growth.

“Since nitrogen is often a major limiting nutrient for crop production, this
interaction allows plants to grow successfully in nitrogen-poor environments
without the addition of costly chemical fertilizers. Ultimately, there has to
be a chemical conversation between the two partners, so our objective is to
understand how this process occurs,” she notes.

The scientists put their heads together and designed a research plan to take
advantage of the beneficial interaction between diverse crops and
growth-promoting bacteria.

“Roots normally forage — just like any herbivore — for a food source, for table water, for competition,” Bais explains. “The interaction with B. subtilis enhances the ability of plants to combat
stresses like disease, drought and nutrient insufficiency. “

The research that Bais and Sherrier are doing with B. subtilis has the potential
to increase biomass — resulting not only in greater yields but also expanded root systems, which can
help plants to tackle abiotic stress, such as a mid-summer drought.

The use of B. subtilis, according to the research duo, is not only less
expensive than utilizing fertilizers, fungicides and supplemental water, but
also has a smaller environmental impact and is straightforward for growers to
implement in both small-scale gardens and large, commercial settings.

This discovery could aid farmers with crop production, as well as help protect
the environment — a combination of benefits that further fuels Bais and Sherrier in their
research.

“I have always been a true believer in doing broad science, answering big and
complex questions related to plant survival and fitness — it is what drives me every day,” Bais says.

Sherrier, who primarily concentrates on fundamental research on plant-microbe
inter-actions, is excited to have collaborated with Bais on this effort and to
apply laboratory results in a field setting.

“When I consider the potential impact of this project for growers, the
environment and on food production, it truly is a dream project for me,” she says.

Aided by UD’s Office of Economic Innovation and Partnerships, from patent procurement
through the commercialization process, Bais and Sherrier hope that B. subtilis
could eventually have a global impact, reaching farming communities in South
America, Australia, Africa and beyond.

Innovation on the rise

UD is the birthplace of such cool technologies as the touch screen in Apple’s iPhone, to vehicle-to-grid (V2G), which allows electric car owners to send
energy stored in their batteries back to the electrical grid, saving money
while helping the environment.

Since the Office of Economic Innovation and Partnerships (OEIP) was formed at
UD in 2008, a key mission of its Technology Transfer Center has been to protect
and commercialize UD researchers’ ideas.

In addition to streamlining the patent process, OEIP has opened it up to the
entire University — anyone from an undergraduate student to a tenured faculty member can disclose
an invention, regardless of its stage of development. OEIP files a provisional
patent on the inventor’s behalf, giving the inventor one year to develop and realize the idea’s commercial potential. During that year, OEIP works closely with the inventor,
providing advice and counsel.

As a result, invention disclosures, the first step in the patenting process,
have increased by more than 60 percent in fiscal year 2010, with 56 filed.

Here’s a look at just a few of these bright ideas:

Marine scientist Mohsen Badiey has two inventions useful for coastal surveying
by autonomous underwater vehicles. One disclosure, called “MIMO,” submitted in collaboration with fellow marine scientist Aijun Song, improves
the accuracy of underwater data transmission. The second prototype provides
accurate position and velocity information for underwater moving objects. When
combined, these two technologies equate to underwater GPS.

Software developed by plant and soil scientist Blake Meyers analyzes and
identifies genes that are regulated in development or in response to stress.
Such genes are useful for introducing special traits in plant biotechnology.

Marine scientist Kathryn Coyne has discovered an algicidal compound capable of
killing harmful dinoflagellates such as Pfiesteria, while having no significant
effect on other algae. There appear to be parallels between the mechanism in
the compound that causes death of the algae, and anti-cancer treatments.

Project managers from OEIP’s Technology Transfer Center are working with each of these professors to
develop commercialization strategies and identify partners to bring the
technologies to market.

﻿Using proprietary algorithms and databases, Adam Marsh’s start-up company, Evozym Biologics, can home in on as few as 50 potentially high-value synthetic proteins from hundreds of billions, saving companies significant time and R&D costs. The company’s target areas are biofuels and antibiotics.

Evozym Biologics Inc., founded in 2009 by scientists at UD and the Desert
Research Institute, aims to accelerate the discovery of useful proteins for the
high-stakes fields of biofuels production and drug development, saving
industries significant time and R&D costs.

Using novel data tools to understand how the genomes of organisms are built,
including high-performance computers and proprietary algorithms and databases,
the Delaware start-up has demonstrated that it can home in on as few as 50
potentially high-value synthetic proteins from hundreds of billions of possible
trajectories, according to co-founder Adam Marsh, associate professor of marine
biosciences at UD.

“Millions of years of evolution have shaped the genes and proteins and enzymes of
microbes, animals and plants,” says Marsh. “Our unique tools understand and systematically utilize these evolutionary rules
of genome adaptation.”

Deriving its name from “evolutionary enzyme,” Evozym Biologics is the brainchild of Marsh, who is on the faculty of UD’s College of Earth, Ocean, and Environment, and Joseph Grzymski, research
assistant professor at the Desert Research Institute in Reno, Nev.

The two first met in Antarctica while doing research on “extremophiles” — organisms that thrive in harsh environments. Marsh does research on sea urchins
in the frigid waters, and Grzymski on microbes that live in both terrestrial
and aquatic polar environments. Both scientists were fascinated by how
organismal genomes can become adapted to life in such difficult, stressful
conditions, and it was this mutual interest that spawned their collaboration.

“That’s the cool thing about science,” Marsh says. “You’ll never know where you’ll end up. I’m working with a marine invertebrate in Antarctica and wanted to know how the
organism’s genome evolved in extreme cold. Joe had a similar interest with microbes that
thrive in high temperatures at hydrothermal vents and in low temperatures in
Antarctica, but was coming at it from another direction. We were working toward
the same goal on two different tracks. When we got together and compared our
findings, every result pointed to success.”

A key to the process, Marsh says, is understanding how specific proteins are
shaped by evolution, by how well they fit into their environment.

In the biofuels realm, a company might spend a million dollars or more on
largely shot-in-the-dark research to identify proteins that are enzymes and
serve as catalysts for certain biochemical reactions, such as breaking down the
cellulose in plant material more easily.

With their computational platform of high-throughput computers and patented
algorithms and databases, Evozym Biologics has zeroed in on a suite of 50 genes
that likely contains several prime candidates for the job, Marsh says.

“The genes we’ve targeted cost only about $1,000 apiece to test,” he notes.

In the drug development arena, the company’s role is to pinpoint a pathogen’s “Achilles’ heel”— its most critical, sensitive genes — so that pharmaceutical companies can create drugs to knock them out.

“Multi-drug-resistant pathogens are a serious issue, causing staph infections,
skin infections and other problems in hospitals and nursing homes,” Marsh notes. “While one drug can target a single protein, a gene often can mutate and bypass
that drug’s effect. But if you could target three to four protein interactions with one
drug, you could build a whole new class of antibiotics.”

Marsh credits the University’s Office of Economic Innovation and Partnerships (OEIP) for helping the company
to protect and organize its intellectual property; OEIP’s Small Business Development Center for advice on how to structure and market
the business; and his dean, Nancy Targett, and associate dean, Chuck Epifanio,
for allowing him to pursue a commercial application of the bioinformatic
discoveries uncovered by his research.

Did Marsh speculate five years ago that he would be leading such a company?

“No way,” he says. “But I really like the idea of bringing research to bear on problems, to make
things better.

“I was so naïve,” he adds. “I thought, ‘ah, we’re done,’ when we got our algorithms completed. But that was just the beginning. I’m excited about the future, and I know we’ll make a difference.”